Autoimmunity is the failure of an organism to recognize its own constituent parts (down to the sub-molecular levels) as “self”, which results in an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease. In order to inhibit harmful immune reactions in such instances, immunosuppressive agents such as corticosteroids and cytokine antagonists may be administered to patients. However these general immunosuppressives can elicit undesirable side effects including toxicity and reduced resistance to infection. Thus alternative, and perhaps more specific, methods of treating autoimmunity are needed.
Several immunomodulatory therapies, including antibody therapies, have proven successful in the treatment of certain autoimmune disorders. However there is a clinical need for additional antibody therapies for the treatment of autoimmune disorders. Furthermore, there is a related need for humanized or other chimeric human/mouse monoclonal antibodies. In well publicized studies, patients administered murine anti-TNF (tumor necrosis factor) monoclonal antibodies developed anti-murine antibody responses to the administered antibody (Exley A. R., et al., Lancet 335:1275-1277 (1990)). This type of immune response to the treatment regimen, commonly referred to as the human anti-mouse antibody (HAMA) response (Mirick et al. Q J Nucl Med Mol Imaging 2004; 48: 251-7), decreases the effectiveness of the treatment and may even render the treatment completely ineffective. Humanized or chimeric human/mouse monoclonal antibodies have been shown to significantly decrease the HAMA response and to increase the therapeutic effectiveness of antibody treatments. See, for example, LoBuglio et al., Proc. Natl. Acad. Sci. USA 86:4220-4224 (June 1989). Furthermore, antibodies in which particular functionalities are either enhanced or reduced may find useful applications in the clinic.
CD200, a molecule expressed on the surface of numerous cell types including B cells, some T cells and dendritic cells and other cells, which possesses a high degree of homology to molecules of the immunoglobulin gene family, has previously been thought to be implicated in immune suppression (Gorczynski et al., Transplantation 65:1106-1114 (1998)). The prior art appears to show, for example, that CD200-expressing cells can inhibit the stimulation of Th1 cytokine production.